This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The regulation of gene transcription process is tightly controlled by the temporal and spatial recruitment of RNA regulatory proteins by the C- terminal domain of RNA polymerase II through its phosphorylation states. Therefore, CTD phosphatases such as human Scp phosphatases can dominate the epigenetic fate of the cell. The crystals we used in this experiments are the complex structures of CTD phosphatases human Scp1 bound to phosphorylated peptides from its substrate, the C-terminal domain of RNA polymerase II with different registration of phosphorylation state. Furthermore, we identified novel inhibitors for Scp phosphatases and seek to obtain structures for protein-inhibitor complex. Such inhibitors can be used to direct neuronal stem cell differentiation.